There is a pressing need for designing new devices facilitating the development of paradigm changing, minimally invasive, approaches to treat diseased tissues in situ. Additionally, there is a growing number of studies showing that combinatorial approaches are providing a path for personalization of strategies to treat a wide array of disease states. While providing a promising path to revolutionize medicine, the evolution of personalized, minimally invasive, combinatorial therapies has been slowed as a result of technological limitations. As such, there is a pressing need for new medical devices to enable the development of trans-disciplinary strategies to combat disease. This Phase 1 project is designed to address this need through the development of a new flexible endoscopic compatible catheter designed for the treatment of various gastrointestinal related tissue diseases enabling the application of multiple therapeutic and diagnostic approaches (pharmaceutical, dual-ablation, cell and gene therapy, among others) in a single device format (FrostBite). The ability to deliver multi- parametric treatment regimes of the FrostBite catheter is enhanced by its compatibility with advanced imaging approaches including endoscopic ultrasound, MRI, and CT. Initial R&D activities have resulted in a prototype 1.5mm needle tip catheter capable of delivering dual thermal insults to a target within 10 seconds creating a zone of destruction of ~2.5cm in less than 2 mins. Preliminary studies into combinatorial drug/thermal insults have shown improved outcomes in tissue models as well. Under this proposal we intend to develop and test this next generation endoscopic compatible catheter as well as evaluate a series of combinatorial strategies. Successful completion of this project will provide for a novel medical device enabling the development and application of advanced personalized treatment regimes for 100's of thousands of patients who suffer from numerous gastrointestinal tissue disease states which are untreatable or inadequately treated with today's state of the art devices.